Repro Flashcards
Canine female hormonal cycle
Proestrus
–> developing follicles release E2 at slowly increasing levels over 9-28d
–> increased blood flow to uterus and vagina which also keratinises
–> after peak starts to fall an LH surge is triggered
Oestrus
–> LH surge marks beginning and matures oocytes
–> ovulation 2 days later along with decreasing E2:P4 ratio)
–> E2 levels decline steadily
–> P4 increases rapidly after ovulation (magnitude determined by number of follicles)
Dioestrus/Luteal Phase
–> Progressive increase in P4 for 2-4 weeks then gradual decrease (regardless of if pregnant) - stays above 5ng until last week of pregnancy
–> Prolactin levels are higher in pregnant bitches
Anoestrus
Phases of oestrus cycle in queen
Seasonally polyoestrous and induced ovulators
Proestrus - <1d duration (rising E2)
Oestrus - 5-7d, shorter if mated and ovulation induced (predominated by oestrus)
Interoestrus - occurs if not mated, lasts 8-9d. Previous follicles regress and new proestrus starts (decrease E2)
Dioestrus - P4 from corpus lutea usually associated with pregnancy but a shortened (45 cf 65d) dioestrus reported in cats that ovulate but do not fall pregnant (pseudopregnancy).
–> more likely to ovulate if multiple matings on single day compared to once.
Anoestrus - lasts several months and is seasonal (shorter days)
Medications to block fertility in Queensgestagins used in Queen fertility control - types and risks
JFMS 2022 review
Progestagins
–> P4 negative feedback to hypothalamus reduces GnRH release –> no LH or FSH
Examples:
Megestrol = most potent, efficacious and minimal long term complications for health - short term studies
higher doses reported to cause DM and adrenocortical impairment
Medroxyprogesterone - has high affinity for P4 receptor but also binds androgen and GC receptors. Can cause increased appetite and weight gain. May see uterine and mammary changes at higher doses
Proligestone - once off SC injection lasts 5 months. May have less affinity for GC and uterine receptors –> fewer side effects
Overdosing can occur if given AFTER ovulation induction (as corpus luteum continues P4 production)
Effect of deslorelin (GnRH analogue) on Queens
Do not just suppress pituitary like progestagins.
GnRH agonists actually initially provide powerful stimulation (positive feedback) to the pituitary causing the release of FSH and LH for up to 2 weeks
The immediate result of the strong gonadotropin secretion caused by deslorelin may or may not be the induction of heat, depending on the stage of the reproductive cycle. Once this phase is over downregulation of pituitary GnRH receptors will occur, causing temporary pituitary desensitisation with suppression of the function of the hypothalamic–pituitary– gonadal axis
in the absence of gonadotropin stimulation, the queen’s ovaries will stop functioning and she will enter anoestrus. Following deslorelin-induced anoestrus, normal fertility has been reported in all investigations
Used to delay onset of puberty
In adult queens, administration of a deslorelin implant will stimulate follicular growth and oestradiol secretion, which is frequently followed by the display of a normal oestrus. This is a fertile oestrus
Use of melatonin in queen reproduction
a neurohormone produced by the pineal gland
Melatonin is released into the general circulation in a continuous fashion, but with greater intensity and reaching higher concentrations during periods of darkness –> max levels in winter
–> this inhibits ovarian function in cats
Common clinical signs/lesions of disorders of sexual development in cats (DSDs)
Any abnormality, anomaly, ambiguity or lesion that occurs because of a failure of development of the female or male reproductive systems
Tricolour male -
Hypospadias - opening of the urethra on the ventral surface of the penis
Ambiguous external genitalia
Female external, internal testis
Testicular abnormalities: anorchia, monorchia, cryptorchidism,testicular aplasia/hypoplasia
Ovarian or periovarian cysts - variety of retained embryonic ducts or tubules, and these may expand and develop into cysts within or near the ovary or uterus. Cysts are derived from either the paramesonephric (future female) or mesonephric (future male) ducts
Segmental uterine absence
Causes of XX genotype with male phenotype
XX ovarian DSD with male phenotype: very rare, caused by deficiency of one of the enzymes responsible for cortisol formation, which leads to excessive testosterone production and congenital adrenal hyperplasia
XX testicular DSD: must be an SRY gene or another gene that produces a product similar to SRY. There are two reports of phenotypic male cats, each with a penis and scrotum but with XX sex chromosomes
DDX for vulvar discharge in dogs
Young dog: split heat, prolonged discharge is common
Older dogs: ovarian neoplasia, endometritis, vaginal tumours
Post-partum: placental subinvolution, infection, retained foetus
Vaginitis - in older dogs more likely due to conformation, FB or neoplasia.
Diagnosis of remnant ovary and recent publications
Clinical signs: oestrogen changes, keratinisation of vaginal cytology
plasma progesterone >2
Antimullerian hormone
AVJ 2018 Sensitivity of antiMH for detection of remnant ovary in prepubertal and adult bitches.
→ Sensitivity 90% if >6 months
Can get false results in entire female dogs.
JAVMA 2019 - combination of P4 + AMH resulted in no dogs with ORS being missed
JFMS 2022 - ORS in Queens had higher AMH than control spayed cats.
GnRH stimulation test
What is cystic endometrial hyperplasia and clinical signficance
An abnormal response of the uterus exposed to repeated long periods of high progesterone concentrations (during the luteal phase) → cyst formation
May also occur with excessive progestagin use
Not all get Pyometra but is considered a predisposing risk factor
Also impairs fertility
Pathogenesis of pyometra
During estrus bacteria from the normal vaginal flora may ascend to the uterus through the open cervix
→ may express virulence factors that enable adherence in endometrium/myometrium and production of toxins such as haemolysins
→ in progesterone stimulated endometrium there is change in protein expression which can enhance bacterial (in particular E.coli) adherence
Principles of medical management of pyometra
Medical:only appropriate if systemically stable and no signs of liver/kidney impairment.
- Open cervix: algepristone (progesterone receptor blocker) is luteolytic +/- dinoprost or cloprostenol (PG agonists)
→ recent review reported 87% recovery rate with medical management, recommend bitches be mated in first season following pyometra.
Types of testicular tumours and potential paraneoplastic effects
Incidence is 68x higher in cryptorchid
Rarely metastasise, and when they do is to local LN first
Interstitial (Leydig)
Seminoma
Sertoli→ paraneoplastic hyperestrogenism → feminisation (may be associated with reduced testosterone:E2 ratio and not necessarily increase in E2. Resolves within 3 months of castration
Rarely causes BM suppression
Types of ovarian tumours and possible paraneoplastic syndromes
Epithelial - more often malignant and 48% metastasis in peritoneal cavity or abdominal LNs
Sex Cord Stromal Tumours - arise from hormone secreting tissue and may be functional (resulting in clinical signs of hormonal excess → oestrus behaviour or excess P4 causing CEH or pyometra), lower metastatic rate
Germ Cell Tumours - arise from primordial cells and include teratomas (which can have any combination of tissues present)
– Ofen have concurrent abnormalities in contralateral ovary and presence of CEH or .pyometra
Lymphoma also reported in cats
Difference b/w uterine neoplasia in cats vs dogs
DOGS: Usually slow growing and non-invasive and non-metastatic.
DDx: GSD cystadenoma and dermatofibrosis
CATS: highly aggressive adenocarcinoma most common and usually metastasis at Dx